This project investigates the roles of autonomic nervous system (ANS activity, attention, and information processing and their interrelationships in the pathology, etiology, and prognosis of psychiatric disorders and studies their underlying biological and psychological processes. ANS activity is assessed by peripheral measures such a skin conductance, heart rate, and skin temperature. Subjects are tested under conditions of rest, presentation of tones, and performance on various tasks, especially reaction time tests of attention. Recent findings: 1) In schizophrenic patients the atypical neuroleptic clozapine, despite greater clinical benefit compared to placebo and conventional neuroleptic, did not improve reaction time measures of attention. However, there was evidence that it increased the efficiency of information processing, and this was mediated by a reduction of hallucinations. 2) A typical neuroleptic with low anticholinergic action, fluphenazine, reduced ANS baselines and selectively attenuated skin conductance orienting responses to simple tones compared to its effects on responses to signal stimuli in a reaction time task. This study shows that some of the markers for schizophrenia reported int he literature may be due to neuroleptic drugs. 3) Adolescents with Childhood-onset Schizophrenia show excessive resting ANS activity but lower than normal ANS activity during a task, low responsivity to novel and meaningful stimuli, and an irregular course of habituation. These results are similar to our previous findings in adult schizophrenics, but even more consistent than the adult data, suggesting that this is a more serve form of the illness. They quite distinct from those seen in other types of child and adult psychopathology. Future plans: Compare the adult schizophrenic group to normal controls, patient with affective disorders, and patients with closed head injuries and frontal lobe lesions tested on the same protocol. Study differences in ANS activity and attention in relation to symptoms. Investigate biological mechanisms by correlating these variables with metabolites of biogenic amines from CFS and with brain structure and activity as revealed by CT,MRI, and PET scans.